We want 1) to define wakefulness in utero in order to assess the influence of fetal behavioral state on breathing; and 2) to discover why the response to hypoxia in neonates consists of transient hyperventilation followed by hypoventilation. In project #1, we will use eye movements, open eyes, head movement and size of mono- and polysynaptic reflexes to define fetal wakefulness. Once this is done, the effect of CO2, cutaneous stimulation, cold stimulation, administration of drugs and other procedures (mid-brain transection) on fetal breathing will be assessed in conjunction with changes in behavioral state. We want to know whether these various stimuli change breathing because of a change in fetal behavioral state. For example, we want to know whether the fetus increases ventilation in response to CO2 before or only when he is awake. Understanding of the factors which induce wakefulness in utero may help us to further understand why the fetus wakes up at the time of delivery. Measurements will consist of electrocorticogram (ECoG), electrooculogram (EOG), tracheal pressure, diaphragmatic EMG, blood pressure and heart rate. Direct observation of the fetus will be made using a fiberoptic device (Olympus, Model BF 3C4). In project #2, acute and chronic experiments will be done in kittens and newborn lambs to know at what level of respiratory control loop hypoxia produces inhibition of breathing. Is it at the peripheral or central chemoreceptor level, at the respiratory muscles or is it a problem of mechanical coupling of the chest wall and abdomen? Measurements will include recording from carotid and phrenic nerve, diaphragmatic and intercostal EMG, esophageal pressure, ventilation, alveolar and arterial gases. In the classic lamb preparation, measurements of behavioral state will include ECoG, EOG, and EMG of the neck muscles. If we discover why hypoxia depresses ventilation early in life, we may understand why breathin is periodic in utero and why apnea is so frequent during the neonatal period.
